A micromaterial in blood such as extracellular vesicles, and the like (altogether hereinafter referred to as EVs), has been recognized in the past as a material with no specific function. However, accumulating evidence suggest that EVs have various biological functions. For example, EVs derived from the platelets have been reported to stimulate a specific cell via selective expression of proteins (e.g. CD154, RANTES, PF-4) on the vesicular surface (Thromb. Haemost. (1999) 82:794; J. Biol. Chem. (1999) 274:7545), and biologically active lipids (e.g. HTET, arachidonic acid) from the platelet-derived EVs have been shown to have a certain effect on their target cells (J. Biol. Chem. (2001) 276:19672; Cardiovasc. Res. (2001) 49(5):88). Taken together, particular characteristics (e.g. size, surface antigens, determination of an origin cell, or payload) of EVs existing in a biological sample can provide information for a diagnosis, prognosis, or treatment of diseases, and, as such, a need for identifying a biological index capable of being utilized for detecting and treating diseases has been well recognized.
Meanwhile, cancer is an incurable disease which is the number one cause of death in most of the industrialized nations presently. A cancer cure rate is still low, and the number of death due to cancer has continuously increased and, in sequence, household burden and national medical expense burden have also significantly increased. Cancer is a disease where cells infinitely proliferate and interfere with functions of normal cells. The representative examples thereof include lung cancer, gastric cancer (GC), breast cancer (BRC) and colorectal cancer (CRC). However, cancer may substantially be generated in any tissue.
In the past, cancer was diagnosed based on external changes in biological tissue caused by growth of cancer cells, but recently, diagnosis and detection of cancer using a trace amount of biomolecules existing in biological tissues or cells such as blood, glycol chain, DNA, or the like, have been attempted. However, the most generally used method for diagnosis of cancer is via usage of a tissue sample obtained by biopsy or usage of an image. Among them, the biopsy has disadvantages in that it causes great pain in patients, requires high expense, and takes a long time for diagnosing cancer. In addition, in a case in which the patient actually has cancer, there is a risk of inducing cancer metastasis during a biopsy procedure, and in a case of a region at which tissue samples through the biopsy may not be obtained, it may be impossible to diagnose a disease before a suspected tissue sample is extracted through a surgical operation. In case of using the image, cancer is diagnosed based on an X-ray image, a nuclear magnetic resonance (NMR) image obtained using a contrast agent having a disease targeting material attached thereto, or the like. However, disadvantages of this type of diagnosis is that there is a probability of a wrong diagnosis depending on proficiency of a clinician or doctor reading the image, and its accuracy is significantly dependent on precision of a device obtaining the image. Further, even in a case of the most precise device, it is difficult to detect a tumor having a size of several mm or less, such that it may be difficult to detect the tumor at an early stage. In addition, since a patient or person with a risk is exposed to a high energy electromagnetic wave which may generate mutation of genes in the process, another disease may be induced. Another disadvantage is that the number of image diagnosis a patient may endure may be limited due to the risk of exposure.
As the biopsy for diagnosing cancer is accompanied by a long time, cost, discomfort, pain, and the like, a method capable of significantly decreasing the number of patients subject to unnecessary biopsy and accurately diagnosing cancer at an early stage is in much demand.
In this regard, the present inventors found that diseases may be diagnosed and predicted by observing morphological characteristics of luterial, which is a type of nanoparticle existing in body fluid of a patient, thereby completing the present invention.